Population specificity of the DNAI1 gene mutation spectrum in primary ciliary dyskinesia (PCD).
Population specificity of the DNAI1 gene mutation spectrum in primary ciliary dyskinesia (PCD).
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DOI：
10.1186/1465-9921-11-174
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发表时间：
2010-12-08
影响因子：
5.8
通讯作者：
Witt M
中科院分区：
文献类型：
--
作者：
Ziętkiewicz E;Nitka B;Voelkel K;Skrzypczak U;Bukowy Z;Rutkiewicz E;Humińska K;Przystałowska H;Pogorzelski A;Witt M
DNAI1 基因（编码睫状体外动力蛋白臂的一个组成部分）的突变是原发性纤毛运动障碍 (PCD) 的第二个最重要的遗传原因，PCD 是一种遗传异质性隐性疾病，患病率约为 1/20,000。已报道的研究对 DNAI1 参与 PCD 发病机制的估计有所不同，范围从 4% 到 10% 不等。 DNAI1 的编码序列在一组 PCD 患者（157 个家庭，185 名受影响个体）中进行了筛选（SSCP 分析和直接测序），这是有史以来第一个研究的大型斯拉夫裔 PCD 患者群体（主要是波兰人）；在大约 80 个家族的子集中进行了多重连接依赖性探针扩增 (MLPA) 分析。在 12 个家族（即大约 8% 的非相关波兰 PCD 患者）中发现了 3 个先前报道的突变（IVS1+2-3insT、L513P 和 A538T）和两个新的错义取代（C388Y 和 G515S）。背景 SNP 单倍型的结构表明了两种最常见突变 IVS1+2-3insT 和 A538T 的共同起源。 MLPA 分析未显示患者和对照样本之间存在任何显着差异。将波兰队列与之前研究的所有 PCD 组（总共 487 个家族）进行比较：IVS1+2-3insT 仍然是 DNAI1 中最常见的致病变化（占全球已发现突变的 54%），而 A538T 全球患病率的增加（14%）是由于波兰队列的贡献。在全球范围内，未预先选择 ODA 缺陷的家庭中，DNAI1 突变参与 PCD 发病机制的比例为 7% 至 10%；这种全球估计以及突变谱在特定人群中有所不同。对背景 SNP 单倍型的分析表明，波兰患者携带 A538T 突变的染色体频率增加可能反映了当地（波兰或斯拉夫）创始人效应。 MLPA 分析结果表明，PCD 发病机制中不涉及大的外显子缺失。
Mutations in the DNAI1 gene, encoding a component of outer dynein arms of the ciliary apparatus, are the second most important genetic cause of primary ciliary dyskinesia (PCD), the genetically heterogeneous recessive disorder with the prevalence of ~1/20,000. The estimates of the DNAI1 involvement in PCD pathogenesis differ among the reported studies, ranging from 4% to 10%. The coding sequence of DNAI1 was screened (SSCP analysis and direct sequencing) in a group of PCD patients (157 families, 185 affected individuals), the first ever studied large cohort of PCD patients of Slavic origin (mostly Polish); multiplex ligation-dependent probe amplification (MLPA) analysis was performed in a subset of ~80 families. Three previously reported mutations (IVS1+2-3insT, L513P and A538T) and two novel missense substitutions (C388Y and G515S) were identified in 12 families (i.e. ~8% of non-related Polish PCD patients). The structure of background SNP haplotypes indicated common origin of each of the two most frequent mutations, IVS1+2-3insT and A538T. MLPA analysis did not reveal any significant differences between patients and control samples. The Polish cohort was compared with all the previously studied PCD groups (a total of 487 families): IVS1+2-3insT remained the most prevalent pathogenetic change in DNAI1 (54% of the mutations identified worldwide), and the increased global prevalence of A538T (14%) was due to the contribution of the Polish cohort. The worldwide involvement of DNAI1 mutations in PCD pathogenesis in families not preselected for ODA defects ranges from 7 to 10%; this global estimate as well as the mutation profile differs in specific populations. Analysis of the background SNP haplotypes suggests that the increased frequency of chromosomes carrying A538T mutations in Polish patients may reflects local (Polish or Slavic) founder effect. Results of the MLPA analysis indicate that no large exonic deletions are involved in PCD pathogenesis.
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影响因子：
9.8
作者：
Guichard, C;Harricane, MC;Bouvagnet, P
通讯作者：
Bouvagnet, P
DOI：
10.1164/rccm.200303-365oc
发表时间：
2004-02-15
影响因子：
24.7
作者：
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通讯作者：
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影响因子：
64.8
作者：
Gibbs, RA;Belmont, JW;Tanaka, T
通讯作者：
Tanaka, T
影响因子：
4
作者：
Failly, M.;Bartoloni, L.;Blouin, J-L
通讯作者：
Blouin, J-L
影响因子：
9.8
作者：
Loges, Niki Tomas;Olbrich, Heike;Omran, Heymut
通讯作者：
Omran, Heymut